Research Investigating Drug Effects-2 (RiDE-2)

Primary outcomes

1. Recent Substance Use

   Time frame: Baseline screening, baseline drug administration, and every 6 months over two years of follow-up

   Participants will complete the 6-month Timeline Follow-Back (TLFB) and Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU) to assess recent substance use. This measure will capture the frequency of substance use during the past 6 months, with greater values indicating more frequent substance use.

2. CUD/SUD Symptoms

   Time frame: Baseline screening and yearly over the two-year follow-up.

   Participants will complete the SCID CUD diagnosis and symptom assessment at baseline screening and yearly follow-ups to evaluate the presence and severity of cannabis use disorder (CUD) and other substance use disorder (SUD) symptoms.

3. Neural Reward Anticipation - fMRI response to reward anticipation (MID)

   Time frame: First and second laboratory visits, around 90 minutes to 2 hours after drug administration.

   Participants will complete the Monetary Incentive Delay (MID) task during fMRI scanning to assess neural activation related to reward anticipation. Greater activation in reward-related brain regions (e.g., striatum, prefrontal cortex) indicates greater neural sensitivity to anticipated rewards and the impact of THC on reward processing.

4. Computationally-Derived Behavioral Reward Learning Rate - Learning rate (alpha parameter)

   Time frame: First and second laboratory visits, around 90 minutes to 2 hours after drug administration.

   Participants will complete the Bandit task during fMRI scanning. A behavioral measure of learning rate (alpha parameter) will be derived from computational models based on the Rescorla-Wagner (RW) model, with higher learning rates indicating greater learning and adaptation to reward contingencies.

5. Computationally-Derived Behavioral Reward Sensitivity - Reward sensitivity (inverse temperature parameter)

   Time frame: First and second laboratory visits, around 90 minutes to 2 hours after drug administration.

   Participants will complete the Bandit task during fMRI scanning, and a behavioral measure of reward sensitivity will be derived from the Rescorla-Wagner (RW) model. Greater values indicate higher sensitivity to rewards and a stronger preference for rewarding outcomes.

6. Neural Encoding of Reward Prediction Errors - fMRI response to reward prediction errors (Bandit Task)

   Time frame: First and second laboratory visits, around 90 minutes to 2 hours after drug administration.

   Participants will complete the Bandit task during fMRI scanning. fMRI analysis will focus on trial-wise neural encoding of prediction errors, with greater activation indicating more salient reward learning signals in response to prediction errors, reflecting how the brain processes unexpected outcomes during reward learning.